The present invention relates to a process for the chiral synthesis of enantiomeric intermediates for the biologically trans hexahydrobenzo[d]naphtho[2,1-b]azepines. These compounds have been disclosed as possessing anti-psychotic, anti-depressant and sedative activities in European Patent Application No. 230270. The synthesis described in European Patent Application No. 230270 produces a racemic mixture of the trans and cis amines. It has been found that the trans amine possesses higher biological activity in general than the cis amine. In addition, one enantiomer of the trans amine possesses considerably greater activity than the other. A chiral synthesis producing only a single enantiomer of the trans amine would therefore increase the yield of the biologically more active enantiomer by a factor of about two.
Stereospecific preparation of amines has been disclosed. For example, Tetrahedron Letters, 1981, 22(28), 2633, describes the asymmetric synthesis of the cis-2-substituted cyclohexamines of the general formula ##STR3## wherein the asterisks indicate chiral centers and the R and NH.sub.2 substituents are in the cis orientation. Also, Bulletin de la Societe Chimique de France, 1970, 12, 4439, describes a study of the reaction products of the asymmetric synthesis of alpha-substituted ethylamines having the general formula ##STR4## wherein the R group is, for example, ethyl or isopropyl. However, these articles do not disclose or suggest that such techniques would be applicable to compounds of the present invention.